A General Strategy to Enhance Donor‐Acceptor Molecules Using Solvent‐Excluding Substituents

While organic donor‐acceptor (D‐A) molecules are widely employed in multiple areas, the application of more D‐A molecules could be limited because of an inherent polarity sensitivity that inhibits photochemical processes. Presented here is a facile chemical modification to attenuate solvent‐dependent mechanisms of excited‐state quenching through addition of a β‐carbonyl‐based polar substituent. The results reveal a mechanism wherein the β‐carbonyl substituent creates a structural buffer between the donor and the surrounding solvent. Through computational and experimental analyses, it is demonstrated that the β‐carbonyl simultaneously attenuates two distinct solvent‐dependent quenching mechanisms. Using the β‐carbonyl substituent, improvements in the photophysical properties of commonly used D‐A fluorophores and their enhanced performance in biological imaging are shown.     

Nanoformulated Single‐Stranded RNA‐Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen‐Presenting Cells

As agonists of TLR7/8, single‐stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off‐target effects or innate immune overactivation. However, low stability prevents them from mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA‐based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group ( CA‐O ) was approximately 100 nm, promoted effective recognition, and improved activation of antigen‐presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA‐O may increase the efficacy of ssRNA‐based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.     

Polymer–Albumin Conjugate for the Facilitated Delivery of Macromolecular Platinum Drugs

The delivery of macromolecular platinum drugs into cancerous cells is enhanced by conjugating the polymer to albumin. The monomers N‐(2‐hydroxypropyl)methacrylamide (HPMA) and Boc protected 1,3‐diaminopropan‐2‐yl acrylate (Ac‐DAP‐Boc) are copolymerized in the presence of a furan protected maleimide functionalized reversible addition‐fragmentation chain transfer (RAFT) agent. The resulting polymer with a composition of P(HPMA₁₄‐co‐(Ac‐DAP‐Boc)₉) and a molecular weight of M_n = 7600 g mol⁻¹ (Đ = 1.24) is used as a macromolecular ligand for the conjugation to the platinum drug. Thermogravimetric analysis reveals full conjugation. After deprotection of the maleimide functionality of the polymer, the reactive polymer is conjugated to albumin using the Cys34 functionality. The conjugation is monitored using size exclusion chromatography, MALDI–TOF (matrix assisted laser desorption ionization time‐of‐flight), and SDS Page (sodium dodecyl sulphate polyacrylamide gel electrophoresis). The polymer–albumin conjugates self‐assemble in water into nanoparticles of sizes of around 80 nm thanks to the hydrophobic nature of the platinum drugs. The albumin coated nanoparticles are readily taken up by ovarian cancer cell lines and they show superior toxicity compared to a control sample without protein coating.

     

A new synthetic route to Mg(2)Na(2)NiH(6) where a [NiH(4)] complex is for the first time stabilized by alkali metal counterions

Mg2Na2NiH6 was synthesized by reacting NaH and Mg2NiH4 at 310 degrees C under hydrogen pressure. The novel structure type was refined from neutron-diffraction data in the orthorhombic space group Pnma (No. 62), with unit cell dimensions of a = 11.428(2), b = 8.442(2), and c = 5.4165(9) Angstrom and a unit cell volume = 523 Angstrom(3) (Z = 4). The structure can be described by (Mg2H2)(2+) layers intersected by (Na2NiH4)(2-) layers. The [NiH4](4-) complex is approximately tetrahedral, indicating formal zerovalent nickel. This is the first example of a solid-state hydride where a [NiH4](4-) complex is directly stabilized by alkali metal ions instead of the more polarizing Mg(2+) ions. A rather long nickel-hydrogen bond distance of 1.65 Angstrom indicates a weaker Ni-H bond as a result of the weaker support from the less polarizing alkali metal counterions.     

Using tolerance intervals in pre-study validation of analytical methods to predict in-study results. The fit-for-future-purpose concept

It is recognized that the purpose of validation of analytical methods is to demonstrate that the method is suited for its intended purpose. Validation is not only required by regulatory authorities, but is also a decisive phase before the routine use of the method. For a quantitative analytical method the objective is to quantify the target analytes with a known and suitable accuracy. For that purpose, first, a decision about the validity of the method based on prediction is proposed: a method is declared proper for routine application if it is considered that most of the future results generated will be accurate enough. This can be achieved by using the "beta-expectation tolerance interval" (accuracy profile) as the decision tool to assess the validity of the analytical method. Moreover, the concept of "fit-for-purpose" is also proposed here to select the most relevant response function as calibration curve, i.e. choosing a response function based solely on the predicted results this model will allow to obtain. This paper reports four case studies where the results obtained with quality control samples in routine were compared to predictions made in the validation phase. Predictions made using the "beta-expectation tolerance interval" are shown to be accurate and trustful for decision making. It is therefore suggested that an adequate way to conciliate both the objectives of the analytical method in routine analysis and those of the validation step consists in taking the decision about the validity of the analytical method based on prediction of the future results using the most appropriate response function curve, i.e. the fit-for-future-purpose concept.     

脂肪胺水溶液吸收CO2的热力学参数的密度泛函理论研究

采用密度泛函理论研究CO₂在脂肪胺水溶液热力学参数．研究的脂肪胺包括烷基胺、链烷醇胺、二胺以及氨基酰胺．在B3LYP/6-311+ G(d,p)水平计算脂肪胺在CO₂气相中的振动频率．通过连续介质模型在HF/6-31G(d)水平计算了溶剂几何优化的标准自由能,评价了CO₂吸收到脂肪胺水溶液过程有关的两个重要参数：酸解离常数和标准焓变二者之间大致呈线性关系．随着胺碱度的提高,CO₂吸收过程释放的热量增加,则胺再生所需的能量增加．     

A Skew Stochastic Heat Equation

We consider a stochastic heat equation driven by a space-time white noise and with a singular drift, where a local-time in space appears. The process we study has an explicit invariant measure of Gibbs type, with a non-convex potential. We obtain existence of a Markov solution, which is associated with an explicit Dirichlet form. Moreover, we study approximations of the stationary solution by means of a regularization of the singular drift or by a finite-dimensional projection.     

The Euclidean Bottleneck Steiner Path Problem and Other Applications of (α,β)-Pair Decomposition

We consider a geometric optimization problem that arises in network design. Given a set P of n points in the plane, source and destination points s, t∈P, and an integer k>0, one has to locate k Steiner points, such that the length of the longest edge of a bottleneck path between s and t is minimized. In this paper, we present an O(nlog² n)-time algorithm that computes an optimal solution, for any constant k. This problem was previously studied by Hou et al. (in Wireless Networks 16, 1033–1043, 2010), who gave an O(n ²logn)-time algorithm. We also study the dual version of the problem, where a value λ>0 is given (instead of k), and the goal is to locate as few Steiner points as possible, so that the length of the longest edge of a bottleneck path between s and t is at most λ. Our algorithms are based on two new geometric structures that we develop—an (α,β)-pair decomposition of P and a floor (1+ε)-spanner of P. For real numbers β>α>0, an (α,β)-pair decomposition of P is a collection $\mathcal{W}=\{(A_{1},B_{1}),\ldots,(A_{m},B_{m})\}$ of pairs of subsets of P, satisfying the following: (i) For each pair $(A_{i},B_{i}) \in\mathcal {W}$ , both minimum enclosing circles of A _i and B _i have a radius at most α, and (ii) for any p, q∈P, such that |pq|≤β, there exists a single pair $(A_{i},B_{i}) \in\mathcal{W}$ , such that p∈A _i and q∈B _i , or vice versa. We construct (a compact representation of) an (α,β)-pair decomposition of P in time O((β/α)³ nlogn). In some applications, a simpler (though weaker) grid-based version of an (α,β)-pair decomposition of P is sufficient. We call this version a weak (α,β)-pair decomposition of P. For ε>0, a floor (1+ε)-spanner of P is a (1+ε)-spanner of the complete graph over P with weight function w(p,q)=?|pq|?. We construct such a spanner with O(n/ε ²) edges in time O((1/ε ²)nlog² n), even though w is not a metric. Finally, we present two additional applications of an (α,β)-pair decomposition of P. In the first, we construct a strong spanner of the unit disk graph of P, with the additional property that the spanning paths also approximate the number of substantial hops, i.e., hops of length greater than a given threshold. In the second application, we present an O((1/ε ²)nlogn)-time algorithm for computing a one-sided approximation for distance selection (i.e., given k, $1 \le k \le{n \choose2}$ , find the k’th smallest Euclidean distance induced by P), significantly improving the running time of the algorithm of Bespamyatnikh and Segal.     

Finger-Knuckle-Print recognition performance improvement via multi-instance fusion at the score level

Fusion of multiple instances within a modality for improving the performance of biometric verification has attracted much attention in recent years. In this letter, we present an efficient Finger-Knuckle-Print (FKP) recognition algorithm based on multi-instance fusion, which combines the left index/middle and right index/middle fingers of an individual at the matching score level. Before fusing, a novel normalization strategy is applied on each score and a fused score is generated for the final decision by summing the normalized scores. The experimental results on Poly-U FKP database show that the proposed method has an obvious performance improvement compared with the single-instance method and different normalization strategies.     

Temperature dependence of coarse-grained potentials for liquid hexane

The present molecular dynamics study is an investigation of the temperature (T) dependence of liquid hexane coarse-grained potentials optimized with the Iterative Boltzmann Inversion method. An approach for the derivation of coarse-grained potentials at temperatures T different from the optimization temperature T(0) has recently been proposed for ethylbenzene. This method is based on the use of a T-dependent scaling factor f(T) to generate ethylbenzene potentials at T≠T(0). The approach is here extended to hexane, considering different reference temperatures T(0) and functional forms for f(T). From our simulations, it appears that the accuracy of the temperature transferability depends simultaneously on the T(0) chosen and the analytic form of f(T). Such a behavior is suppressed by the use of a new 2-point interpolation formula to generate coarse-grained potentials as a function of T. This scheme employs a linear interpolation based on the optimization of coarse-grained potentials at two reference temperatures, T(L) and T(U), with T(L)≤T≤T(U). Accurate coarse-grained simulations of liquid hexane can be performed using the new interpolation scheme. The results are encouraging for the use of potential interpolations as a practical means for devising coarse-grained potentials within a wider temperature range.